Exam 1 - PK/PD Flashcards
How many receptors need to bound to acheive the greatest effect?
Example?
- All receptors bound
- Paralytics (we want total paralysis, not partial)
What are the 3 ways that drugs bond to receptors?
What type bonding is irreversible?
- Ionic, Hydrogen, Van der waals
- Covalent
Differentiate competitive vs non-competitive antagonism?
- Competitive: giving more agonist will overcome antagonistic effects
- Non-competitive: no amount of agonist will overcome antagonistic effects (insurmountable)
What is a partial and inverse agonist?
Examples of inverse agonists?
- Partial: has less effect than full agonist even in higher doses
- Inverse: binds at active site but causes an opposing effect from the agonist (propanolol, metoprolol, cetirizine, loratidine, prazosin, naloxone)
Upregulation vs downregulation?
Upregulation: receptors increase in number due to low level of ligand (more sensitive)
Downregulation: receptors decrease in number due to high levels of ligand (less sensitive)
What is tachyphylaxis?
What 2 drugs undergo this?
What condition?
Tachyphylaxis: Rapid tolerance to a drug produce diminishing effects with each administration
- Albuterol (receptors downregulate due to repetition)
- Ephedrine (depletion of stored presynaptic catecholamines with each dose)
- Pheochromocytoma (decreased β receptors in response to catecholamines)
What drugs bind to intracellular receptors?
- Insulin
- Steroids
- Milrinone
What drug class binds to circulating proteins?
Anticoagulants (Warfarin)
What is the vessel rich group?
Bolused drugs first distrubute to tissues that receive the bulk of arterial blood flow: the brain, heart, kidneys, and liver.
What is meant by a high and low VD?
High: drug distributes out of blood to tissue quickly - (lipid soluble drugs)
Low: drug stays within the cardiovascular system - (water soluble drugs)
What proteins do acidic and basic drugs bind to?
Acidic = Albumin
Basic = ⍺1-acid glycoprotein
Why do we care if drugs are bound or not?
- Protein bound drugs are not available to interact with their receptors
- Only unbound drugs can cross cell membranes
What factors/conditions can decrease plasma protein concentrations?
- Age
- Liver dx
- Renal failure
- Pregnancy
- Burns
- Acidosis
- Malnutrition
If a drugs normal free fraction is 2% and their albumin is dropped by half, what is the new free fraction?
What does this mean?
- 4%
- This means with the same dose, the patient may have double the effect which usually comes with undesirable effects
What drugs have a high VD?
Why?
- Thiopental, diazepam, propofol
- They are poorly protein bound and lipophilic
What drug has a low VD?
Why?
- Warfarin
- It is highly protein bound
What are the Phase I reactions?
What is their purpose?
- Oxidation, Reduction, and Hydrolysis
- Increases drug polarity to make them more water soluble in preparation for elimination
What is the phase II reaction?
What does it do?
- Conjugation
- Links covalently with a polar molecule to become more water soluble
What does it mean when CYP enzymes have more letters/number?
What is the most common CYP enzyme for anesthetic drugs?
- The enzyme group is more specific
- CYP3A4
Describe enzyme induction and inhibition?
Examples?
Induction - increases activity of enzyme → increases drug metabolism → decreases drug effects (phenobarbital)
Inhibition - decreases activity of enzyme → decreases drug metabolism → increases drug effects (grapefruit juice)
Hepatic clearence is ⎽ for most anesthetic drugs?
Constant
What is flow limited clearance?
- Rate of clearance is proportional to drug concentration
- More hepatic flow = more clearance
What is capacity limited clearance?
- Liver metabolism is the limiting factor for drug clearance
- Only a certain amount can be cleared, regardless of changes in flow
Describe the 3 processes that govern renal clearance?
- Filtration: glomerulus → tubule
- Secretion: PT capillaries → tubule (active transport)
- Reabsorption: tubule → PT capillaries (increased for lipid soluble drugs)